Using optical mapping, electrophysiological changes were compared between Langendorff-perfused Pak2cko and Pak2f/f hearts. Under baseline conditions, there was no difference in the incidence of ventricular arrhythmias between the two groups. However, acute isoproterenol stimulation increased the incidence of ventricular tachycardia (VT) in Pak2cko hearts, and Pak2cko/TAC hearts exhibited an even higher incidence of ventricular arrhythmias.

A) Flow chart of optical mapping scheme. B) VT inducibility in ex vivo Langendorff hearts after TAC challenge in Pak2f/f and Pak2cko mice. C) Heat maps (indicating the spectral intensity differences of Ca2+ transients) showing frequency-dependent CaT alternans during progressive decrements in cycle length between 100–70 ms. The corresponding CaT traces are also exhibited from the selected region within the boxes. D) Calculation of CaT alternans ratio for each group (n = 6 hearts for each group). Large alternans ratio (>20%) are counted for evaluation of the severity of CaT alternans. E) Typical AP traces during VT induced by progressive pacing; the activation map shows that the initiation positions for ectopy and reentry overlap with regions harboring the most severe AP alternans. F) Typical consecutive phase maps during VT in a Pak2cko mouse heart, showing the fast re-entry rotors meandering on the epicardium without losing the coupling of AP and CaT, along with the corresponding AP and CaT traces. *p < 0.05, **p < 0.01, ***p < 0.001.

Advanced science  (IF  14.1)

DOI: 10.1002/advs.202411987